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CD137L and CD4 T cells limit BCL6-expressing pre-germinal center B cell expansion and BCL6-driven B cell malignancy.
- Source :
-
Immunology and cell biology [Immunol Cell Biol] 2022 Oct; Vol. 100 (9), pp. 705-717. Date of Electronic Publication: 2022 Aug 17. - Publication Year :
- 2022
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Abstract
- Aberrant expression of the proto-oncogene BCL6 is a driver of tumorigenesis in diffuse large B cell lymphoma (DLBCL). Mice overexpressing BCL6 from the B cell-specific immunoglobulin heavy chain μ intron promoter (Iμ-Bcl6 <superscript>Tg/+</superscript> ) develop B cell lymphomas with features typical of human DLBCL. While the development of B cell lymphoma in these mice is tightly controlled by T cells, the mechanisms of this immune surveillance are poorly understood. Here we show that CD4 T cells contribute to the control of lymphoproliferative disease in lymphoma-prone Iμ-Bcl6 <superscript>Tg/+</superscript> mice. We reveal that this CD4 T cell immuno-surveillance requires signaling by the co-stimulatory molecule CD137 ligand (CD137L; also known as 4-1BBL), which may promote the transition of pre-malignant B cells with an activated phenotype into the germinal center stage via reverse signaling, preventing their hazardous accumulation. Thus, CD137L-mediated CD4 T cell immuno-surveillance adds another layer of protection against B cell malignancy to that provided by CD8 T cell cytotoxicity.<br /> (© 2022 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
- Subjects :
- Animals
CD4-Positive T-Lymphocytes metabolism
Germinal Center metabolism
Humans
Immunoglobulin Heavy Chains
Mice
Proto-Oncogene Proteins c-bcl-6 genetics
Proto-Oncogene Proteins c-bcl-6 metabolism
4-1BB Ligand metabolism
Lymphoma, Large B-Cell, Diffuse genetics
Lymphoma, Large B-Cell, Diffuse metabolism
Lymphoma, Large B-Cell, Diffuse pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1711
- Volume :
- 100
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Immunology and cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 35916066
- Full Text :
- https://doi.org/10.1111/imcb.12578